Evaluation of the Efficacy and Safety of Nicotinamide in Non-Alcoholic Fatty Liver Disease Patients

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, with increasing prevalence as a consequence of the pandemic spread of obesity and diabetes. It is emerging as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. Patients with NAFLD have an increased risk of developing cardiovascular diseases, cirrhosis, liver failure, hepatocellular carcinoma, and impaired quality of life (QOL), but there are currently no licensed therapies for NAFLD. Nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2D) are strongly associated and approximately 60% of patients with T2D have NAFLD. Nicotinamide has been reported to protect against liver steatosis and metabolic imbalances in NAFLD in animal models through nicotinamide adenine dinucleotide (NAD+) boosting. Increasing NAD+ levels activates sirtuins expression and signaling pathways causing inhibition of lipogenesis and activation of fatty acid oxidation. Moreover, nicotinamide riboside was found to improve glucose control, decrease hepatic steatosis, hypercholesterolemia, and liver damage in insulin-resistant mice raised on high-fat diet. Therefore, the American Association for the study of liver disease has recommended initiating clinical trials to evaluate the benefits of nicotinamide in NAFLD patients. Objectives: To investigate the efficacy and safety of nicotinamide supplementation in diabetic NAFLD patients. Design: A prospective randomized controlled open label study conducted on Egyptian diabetic NAFLD patients. Methods: Seventy diabetic NAFLD patients were randomly assigned either to nicotinamide group (n=35) who received nicotinamide 1000 mg once daily for 12 weeks in addition to their anti-diabetic therapy or control group (n=35) who received their anti-diabetic therapy only. Patients were included if f they met the following criteria: age between 18 to 65 years old, diagnosis with T2D, having controlled attenuation parameter (CAP) score (> 248 decibels per meter (dB/m)) with or without liver enzyme elevation and receiving sulfonylurea or metformin or both with stable regimen for at least 4 weeks prior to participation in the study. Exclusion criteria were as follows: having cirrhosis, hyper / hypoparathyroidism, cancer, viral hepatitis, biliary disease, other causes of liver disease (hemochromatosis, Wilson’s disease), encephalopathy or variceal bleeding, ascites, congestive heart failure and renal impairment, receiving statins, hepatotoxic medicines and/or medications with evidence for effects on NAFLD within 6 months before the start of the study and during the study and being pregnant or lactating. The primary outcome was the improvement in steatosis score utilizing CAP technique, while secondary outcomes included assessment of liver stiffness utilizing liver stiffness measurement, liver enzymes, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), serum malondialdehyde as a marker of oxidative stress, serum adiponectin, patients’ QOL using chronic liver disease questionnaire and nicotinamide safety.